Overexpression of Nerve Growth Factor in Skin Increases Sensory Neuron Size and Modulates Trk Receptor Expression

Goodness, Thomas P.; Albers, Kathryn M.; Davis, Frankie; Davis, Brian M.

doi:10.1111/j.1460-9568.1997.tb01515.x

Cited by 64 publications

(38 citation statements)

References 62 publications

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“…This assumption is supported by data from NGF transgenic animals where NGF gene is over expressed in skin (Davis et al, 1994). Sympathetic nerve terminals form baskets around trkA expressing sensory neurons in the NGF transgenic mice (Davis et al, 1998;Goodness et al, 1997). Over expression of NGF in glial cells also induces allodynia and enhances sympathetic sprouting around large diameter neurons after a nerve lesion (Ramer et al, 1998).…”

Section: Discussionmentioning

confidence: 83%

BDNF is involved in sympathetic sprouting in the dorsal root ganglia following peripheral nerve injury in rats

1999

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Peripheral nerve injury results in sympathetic sprouting around large diameter sensory neurons in the dorsal root ganglia (DRG). The mechanism underlying this pathological phenomenon is not known. Brain-derived neurotrophic factor (BDNF) is upregulated in large sensory neurons and ensheathing satellite cells following a sciatic nerve injury. In the present study, we investigated the effects of BDNF on the sympathetic sprouting in the DRG, by delivering BDNF antibody or antisense oligodeoxynucleotide to injured DRGs, or by delivering exogenous BDNF to intact DRGs. The sheep antibody to BDNF, characterized by bioassays and dot blots, specifically reacted with BDNF but not other neurotrophins. Noradrenergic fibres were visualized by immunostaining of tyrosine hydroxylase (TH) and quantified by an NIH Imaging program. Two weeks following L5 spinal nerve lesion, a dramatic increase in TH-immunoreactive (-ir) fibres was observed in both ipsi-and contralateral DRGs in normal sheep IgG treated rats. BDNF antibody significantly reduced the sprouting of sympathetic nerves in both ipsi-and contra-lateral DRGs by 67% and 42% respectively. BDNF antisense oligodeoxynucleotide, by inhibiting BDNF synthesis in DRGs, also significantly suppressed the sprouting by 67% and 60% respectively in the ipsi-and contralateral DRGs. Delivery of exogenous BDNF into an intact L5 DRGs resulted in an increase in the sprouting by 4.2-fold. Our results clearly indicate that BDNF, synthesized in and secreted from the DRGs, is involved in the sympathetic sprouting in the DRG following the peripheral nerve injury.

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Section: Discussionmentioning

confidence: 83%

BDNF is involved in sympathetic sprouting in the dorsal root ganglia following peripheral nerve injury in rats

1999

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“…Somal hypertrophy and hyperexcitability of nociceptive afferent neurons have also been demonstrated in rats with chemically induced ileitis (Moore et al, 2002). Moreover, in previous studies using NGF overexpression transgenic mice, mRNA levels of Na v 1.8 as well as Na v 1.9 were significantly increased, although the TTX-resistant Na ϩ current density was not changed in DRG neurons, which had larger somata, compared with wild-type mice (Goodness et al, 1997;Fjell et al, 1999). Thus, it could be speculated that long-term exposure of NGF has a role in the maintenance of cell excitability by distributing TTXresistant Na ϩ channels over a larger surface area of hypertrophied sensory neurons.…”

Section: Discussionmentioning

confidence: 98%

Bladder Overactivity and Hyperexcitability of Bladder Afferent Neurons after Intrathecal Delivery of Nerve Growth Factor in Rats

Yoshimura¹,

Bennett²,

Hayashi³

et al. 2006

J. Neurosci.

153

170

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Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 g/l) was infused continuously into the intrathecal space at the L6 -S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 l/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6 -S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K ϩ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K ϩ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

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“…The local production of NGF regulates cell body size, axonal sprouting and dendritic arborization [15,16]. In agreement with this, transgenic mice overexpressing NGF in epithelial structures show changes in neuronal phenotype associated with a striking increase in the number of axons, an altered distribution and enhanced branching of fibers in target organs [17,18,19,20]. …”

Section: Introductionmentioning

confidence: 85%

NGF and Its Receptors in the Regulation of Inflammatory Response

Minnone

Benedetti

Bracci-Laudiero

2017

IJMS

227

163

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There is growing interest in the complex relationship between the nervous and immune systems and how its alteration can affect homeostasis and result in the development of inflammatory diseases. A key mediator in cross-talk between the two systems is nerve growth factor (NGF), which can influence both neuronal cell function and immune cell activity. The up-regulation of NGF described in inflamed tissues of many diseases can regulate innervation and neuronal activity of peripheral neurons, inducing the release of immune-active neuropeptides and neurotransmitters, but can also directly influence innate and adaptive immune responses. Expression of the NGF receptors tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) is dynamically regulated in immune cells, suggesting a varying requirement for NGF depending on their state of differentiation and functional activity. NGF has a variety of effects that can be either pro-inflammatory or anti-inflammatory. This apparent contradiction can be explained by considering NGF as part of an endogenous mechanism that, while activating immune responses, also activates pathways necessary to dampen the inflammatory response and limit tissue damage. Decreases in TrkA expression, such as that recently demonstrated in immune cells of arthritis patients, might prevent the activation by NGF of regulatory feed-back mechanisms, thus contributing to the development and maintenance of chronic inflammation.

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Overexpression of Nerve Growth Factor in Skin Increases Sensory Neuron Size and Modulates Trk Receptor Expression

Cited by 64 publications

References 62 publications

BDNF is involved in sympathetic sprouting in the dorsal root ganglia following peripheral nerve injury in rats

BDNF is involved in sympathetic sprouting in the dorsal root ganglia following peripheral nerve injury in rats

Bladder Overactivity and Hyperexcitability of Bladder Afferent Neurons after Intrathecal Delivery of Nerve Growth Factor in Rats

NGF and Its Receptors in the Regulation of Inflammatory Response

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